Objective To test the hypotheses that insulin acts in the brain to inhibit food intake and increase metabolic rate, and that NPY has opposite effects. Insulin and insulin receptors are present in the CNS, but neurons, unlike most peripheral tissues, do not require insulin for glucose uptake. Insulin is believed to be involved in the regulation of energy balance through actions upon hypothalamic structures. In order to evaluate these effects, exogenous insulin was administered to young adult male rhesus monkeys via indwelling cannulae placed in the lateral cerebral ventricle (LCV). (This project represents largely the research performed by Dr. Wolden-Hanson for her Ph.D. dissertation, which was completed under Dr. Kemnitz's supervision during this report period.) Three experiments were conducted to assess the acute effects of a range of insulin doses on food intake. The effect of chronic insulin infusion was evaluated in a fourth experiment. Insulin reliably suppressed food intake when administered twice per day or continuously. There was no effect of insulin on pattern of food intake, or on body weight, physical activity or oxygen consumption. Results suggest the central insulin has a role in the control of food intake, but not energy expenditure, under these experimental conditions. Four of these monkeys were subsequently given NPY in various doses via the LCV cannula. Results indicate no effect of low doses of NPY, a stimulation of eating at moderate doses and a suppression of intake at the highest dose. These preliminary data will be used to design studies of antagonists of NPY that could be useful to combat obesity in humans. Key words food intake, hypothalamus, insulin, neuropeptide Y